The regulatory mechanisms involved in the induction of hepatic malic enzyme by a marked restriction in the amount of dietary protein will be studied in conjunction with the possible functions fulfilled by this particular enzyme under the same experimental conditions. Several different experimental approaches will be used to study these two facets of hepatic malic enzyme; among these will be the application of cultured minimal deviation hepatoma cells as a model for studying the effects of hormones and nutrients on the regulation of enzyme steady-state concentration, the use of isolated hepatocytes to determine metabolic events in the liver of animals maintained on a normal or low protein diet, and the measurement of the activity of pyruvate carboxylase in the livers obtained from the different experimental animals. Possible changes in the total carboxylation rate associated with modifications of malic enzyme and pyruvate carboxylase activities will also be examined. It is expected that these investigations will yield important information regarding the mechanisms of induction and regulation of an enzyme in a mammalian liver cell as well as the particular metabolic functions of malic enzyme under non-lipogenic conditions.